Cancer screening: serum Protein levels – Flashcards
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Serum and Plasma Proteins
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There are both in our body 2 serum; Albumin and Globulin. Albumin is a single protein,Globulin has 5 types alpha, beta and gamma Plasma proteins are involved in clotting: Fibrinogen and prothrombin
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Serum Albumin
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Is a blood plasma protein that is synthesized by the liver. Liver issues can decrease albumin. Single most abundent protein in our plasma. Function of Albumin is to transport hormones including Thyroid estrogen and cortisol. Transports drugs like warfarin and penicillin. Maintains oncotic pressure, so a decrease in albumin will cause edema due to imparied intravascular oncotic pressure. Due to kidney disease diabetes and other diseases
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Why draw an albumin level
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Helps determine liver or kidney disease or if our body is not absorbing enough protein Indications for testing: Jaundice, fatigue, weight loss or symptoms of nephrotic syndrome
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Why would you have DECREASED levels of albumin
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Decreased production; Low protein diet, malnutrition, malabsorption. Cirrhosis of liver Excess excretion by kidneys such as ascites, protein losing nephropathy or enteropathy. Excess dumping Prolonged diarrhea Skin burns
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Limitations to the testing of Albumin
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Decreased in pregnancy Large amounts of IVF will skew results Check BUN and creatinine to assess renal function at same time Pre albumin to assess nutritionsl Marked lipemia or fat in blood will skew results
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How do we measure Serum and plasma proteins
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Electrophoresis Immunoelectrophoresis Immunofixation
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Electrophoresis
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procedure that is used to determine amounts of albumin and 5 globulins by counting them out
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Immunoelectrophoresis
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If certain gamma globulins are abnormal you need to do this test to separate the 5 types IgG IgA IgM IgD or IgE Immunofixation: simmilar to this
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SPEP: Serum protein electtrophoresis
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measures the albumin and globulin proteins. Albumin is the major component of the serum Range: Albumin: 3.3-5.7 g/gl Alpha 1: 0.1-0.4 Alpha 2 0.3-0.9 Beta 2 : 0.7-1.5 g/dl Gamma: 0.5-1.4 g/dl
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Albumin Interpretation
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Range 3.3-5.7 g/dl Increased: severe dehydration Decreased: Malnutrition, cachexia, liver disease, nephrotic syndrome, protein losing enteropathies or severe burns
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Alpha 1 interpretation
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Range: 0.1-0.4 g/dl Increased: Inflammatory states, pregnancy Decreased: Alpha 1 antitirypsin deficiency
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Alpha 2 interpretation
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Range: 0.3-0.9 Increased: Inflammatory state, nephrotic syndrome, OCP use, Steroid use or hyperthyroid Decreased; Hemolysis and Liver disease
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Beta Interpretation:
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0.7-1.5 g/dl Increased: Hyperlipidemia, IDA Decreased: Hypo beta lipoproteinemia and malnutrition
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Gama Interpretation
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Range 0.5-1.4 g/dl Increased: Polyclonal and monoclonal gammapathies Decreased: Agammaglobulinemia, hypogammaglobulinemia
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Monoclonal Protein
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Always abnormal: Secreted by an abnormally expanded clone of plasma cells. AKA M protein, M-component Indicates plasma cell disorder; Lymphoid malignancies, Chronic Leukemia lymphoma, B or T cell lymphmas, breast cancer, colon cancer, cirrhosis, sarcoid or other autoimmune disorders
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Multiple Myeloma and Monoclonal Protein
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Remember m protein is abnormal Multiple Myeloma is a cancer of plasma cells in bone marrow Normal plasma cells produce antibodies or immunoglobulins that fight infection. Each plasma cells produce 1 type of immunoglobulin. In MM, the plasma cell alpha clone is duplicated in large numbers and causes excess production of monoclonal mprotein
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Increased monoclonal gamma proteins means
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Multiple myeloma, smodering myeloma, MGUS, POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes, etc Need hematologist...to figure out
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Polyclonal Gammopathy: What does it mean
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Broad based peak or spike in the gamma region Infectious, inflammatory, or various reactive processes can cause elevation Such as Liver Disease: Cirrhosis, autoimmune or viral hepatitis Connective Tissue disease: RA, SLE, scleroderma, Sjogren syndrome Infection: Bacterial: osteomyelitis, endocarditis. Viral: HIV, hepatitis EBV Hematologic: NHL, Chronic Leukocytic Leukemia, thalassemai and Sickle cell anemia Non Hematologic: Malignancies such as Lung, ovarian, gastric, hepatocellular carcinoma
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SPEP considerations when reviewing and ordering
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Can miss detection of M protein due to low Number If you suspect a clonal plasma issue order serum immunofixation and or free light chain assay
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Why would you order a SPEP
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In any pt with elevated total protein, especially wiht elevated globulin level related to albumin or underlying plasma cell disorder. Unexplained anemia, back pain, bone pain or fatigue Unexplained pathologic fracture or lytic lesion Unexplained peripheral neuropathy Hypercalcemia secondary to malignancy Hypergammaglobulinmia CKD with bland urine sediment Unexplained Proteinuria
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Immunofixation Test
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Consists of electrophoresis and fixation phase: Normal Negative for monoclonal protein and polyclonal protein Polyclonal + considered nonspecific Should not see oligoclonal bands Will be 1 of 3: Normal pattern, monoclonal protein pattern or polycolonal immunoglobulin pattern Can be a Urine (24 hour) Plasma or CSF specimen
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Immunofixation interpretation and monitoring therapy
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See if M protein is decreasing during chemo therapy Is the primary screening for plasma cell dyscrasias Used for surveillance for pt with MGUS or asymptomatic smoldering MM (URine) A negative serum or urine immunofixation does not always rule out plasma cell dycrasias need serum free light chain ratio
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Immunofixation and identifying a monoclonal immunoglobulin disorders:
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MGUS Multiple myeloma Waldenstrom macroglobulinmia Amyloidosis
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Oligoclonal Bands in the CSF in Immunofixation interpretation
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Diagnosis of: Multiple sclerosis Neurosyphillus, HIV encephalitis Neruosarcoidosis Lyme meningitis SLE Sjogren syndroms CNS malignancy Transverse myelitis
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Free Light Chain:
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Normal immunoglobulins are composed of smaller units. Heavy and light chains that form a larger complex. Heavy: IgG, IgA, IgM IgD and IgE Light: Kappa and Lambda Each plasma cell produces 1 heavy and 1 light. Ex. IgG kappa IgG Lamda Heavy and light chains are formed seperately but combine to form and whole immunoglobulin
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Free light chains and mylomas
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Light chains are attached to heavy chains: bound light chains Light chains not attached are : free light chains Plasma cells produce more light chains than needed or form whole immunoglobulins or monoclonal proteins and the excess light chains enter the bloodstream as free light. The amount of free light chain is linked to the activity of myeloma or plasma cell growth. (which one IgG etc)
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What do Serum Free Light chain Assay tell you
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Sensitive and specific for various light chain associated disorders Need to order SPEP, IFE and serum free light chain to detect intact immunoglobulins and free light chains Useful in monitorin response to therapy Can detect midldly elevated levels of free light: early disease Urine not as good but good for AL amyloidosis
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Serum Free Light Chain Assay: FLC, Freelite
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Normal values: Kappa: 3.3-19.4 mg/l Lamda: 5.71-26.3 mg/L Kapp/Lamda ratio: 0.26-1.65. Renal dysfunction: 0.37-3.1 Check Ratio: If Kappa/Lamda high and the other low: Active myeloma If both are high usually indicates another disease like kidney dysfunction *** Myeloma cells are Kappa or Lambda
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UPEP: Urine Protein electrophoresis and immunofixation
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Similar to SPEP but Urine 24 hour collection Diagnosis: Pt who have light chain secretion only. Kidneys filter the blood leaving most of the protein in our blood, so normal UA will show no trace of protein. When a monoclonal protein is present in the serum there is excess of free light chains in urine called BENCE JONES PROTEIN. UPEP looks for Bence Jones Protein. If seen is abnormal will need IFE to identify which type of protein
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Tumor Markers
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Substances that are associated with malignant cell growth
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AFP: alpha Fetoprotein
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Normal in yolk sac and liver of fetus. Trace amount after birth AFP testing in amniotic fluid for defects: congenital and Downs Non pregnant women and men: Marked elevation are associated with primary carcinoma of liver and some testicular cancers.
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B2M: Beta-2 Microglobulin
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Light chain protein found on cell walls. Elevated in: Multiple Myeloma Chronic lymphocytic leukemia Some lymphomas Hepatitis Crohns or chronic inflammatory states
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CEA: carcinoembryonic Antigen
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Glycoprotein Elevated in malignant tumors of Colon Cancer metastatic breast cancer Most useful in evaluating response to therapy: Should see decrease. Not a value in diagnosing colon cancer
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Ca 125 ANTIGEN
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Tumor marker used in diagnosis and managing of ovarian cancer Women will have elevated levels but is not a screening tool because of lack of sensitivity
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CA 125 Antigen and its indications
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Ovarian cancer Endometrial carcinoma or endometriosis Cirrhosis Endocervical adenocarcinm Do if you have a pelvic mass Response to therapy Detection of recurrence Determine Prognosis Early detection of hereditary syndrome
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HBOS: Hereditary Breast and ovarian cancer syndrome
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Persons with mutations in BRCA a or 2 have HBOS Risk of CA increase up to 60% pt will have salpigo oophorectomy as prevention: if not transvaginal q 6 months or 5-10 years from earliest diagnosis
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Ca15-3 Ca 27.29
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Both are breast cancer markers 15-3 breast cancer high levels can be seen in pt with breast cancer mets both will rise befroe clinical evidence of relapse
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HER-2/neu
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Human epidermal growth factor receptor 2 over expressed in some tumors used to guide therapy for breast CA treatment. Looks at estrogen and progesterone receptors. Helps guide therapy
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PSA prostate specific antigen
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Measure the amount of PSA in blood Biomarker for prostate CA Men w/o history of Ca start at 40 elevated PSA: watchful wating PSA Pretreatment prostate ca screening treatments
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Free PSA
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2 forms in human blood bound and unbound bound attached to proteins PSA can be elevated in BPH Free PSA is elevated in prostate Ca